Rose McGowan was next rumored to take leading roles in Robert Rodriguez' Barbarella and Sin Ciy 2 and was officially announced to star in Black Oasis as the 1950s B-movie queen Susan Cabot. Unfortunately, the film was one of the many affected by the writer's strike and like Barbarella and Sin Ciy 2, it was put on hold. Director Stephan Elliott moved on to film Easy Virtue, starring Jessica Biel and Colin Firth, while Rose herself embarked on a whole different journey: the role of Grace, a woman who is in the highest level of the IRA in Fifty Dead Men Walking. The movie was filmed in Ireland and saw Rose act alongside veteran actor Sir Ben Kingsley and up and comer Jim Sturgess. Fifty Dead Men Walking premiered at the Toronto Film Festival in September 2008 and was released in the UK in April 2009 with warm reviews.

Miss McGowan, a great lover of the Golden Age of Hollywood, appeared as a Guest Programmer on Turner Classic Movies in November 2007. Rose co-hosted a series of her favorite films with TCM's Robert Osborne. Her enthusiasm impressed the heads of TCM so Rose's one-time gig developed into a full series, The Essentials, which she again co-hosted with Osborne. "During our many shoots with Guest Programmers this year, we encountered a lot of celebrities who impressed us with their knowledge and love of classic film," said Tom Brown, vice president of original programming for TCM. "But Rose really stood out, because she was so passionate and insightful. We thought it would be great for her to share her passion with the audience by co-hosting The Essentials in 2008." Says Rose herself: "When they called me up to do this, I was just thrilled. I didn't even know I was going to get paid. I was so excited, I would have done it for free." The Essentials kicked off March 8, 2008.

McGowan filmed a guest stint for the FX network's Nip/Tuck between 2008 and 2009. Rose replaced Katee Sackhoff in the role of Theodora "Teddy" Rowe, a villainous doctor and love interest for Sean (Dylan Walsh), for five episodes during the show's sixth season. The role was a different role for Rose and the actress was able to show her versatility and subtle acting quality in a role that could very easily have been over the top if played by another. Rose also filmed a cameo for Robert Rodriguez's Machete, an expansion of the fake trailer that he created for Grindhouse.

Next Rose McGowan geared up for something else entirely; indie film Dead Awake (aka Dylan's Wake) and the role of Charlie, a homeless schizophrenic crackhead who finds friendship with Nick Stahl's Dylan. It is the story of a young man who fakes his own death to see if anyone will show up at his funeral. Two people show up – a street junkie who believes the protagonist is an angel who has come to save his life, and his high school sweetheart (Amy Smart) from ten years before. Their lives will be changed forever in this supernatural film about friendship, romance and redemption. "I'm having an amazing and fulfilling time," Rose said on the set of the film. "I love my castmates, the director and the kindest producers I've ever worked with." The film will be available on DVD in November 2010.